Artificial Intelligence, Genuine Outcome: Analysis of 72 Consecutive Cases of Subfascial Augmentation Mastopexy With Smooth Round Implants Supported by P4HB Scaffold.

BACKGROUND: Ptosis recurrence often leads to unsatisfactory results after mastopexy, even more so when additional stress is provided by implants on compromised native tissue. Poly-4-Hydroxybutyrate(P4HB) scaffold(GalaFLEX) with its favorable safety profile and proven long-term mechanical strength represents a preferred option for soft-tissue support. OBJECTIVES: Primary endpoint was to assess lower pole stretch from early post operative time up to 3 years. METHODS: Out of 151 patients operated by the first author from March 2020 to December 2023, a total of 72 with 12-month-mininum follow-up undergoing primary(46) or secondary(26) augmentation mastopexy with subfascial round smooth implants and P4HB scaffold support were included in the study. A 3-D artificial-intelligence (AI) software was used for all measurements. Further analysis included evaluation of ptosis recurrence and all complications. RESULTS: No recurrent ptosis, bottoming out, implant displacement or capsular contracture were reported during follow up (mean 24.8 months). Lower pole arch's elongation was 8.04% and 9.44% at 1 and 3 years respectively, comparing favorably with previous reports. Statistically significant correlation (p < 0.05) between implant size and lower pole stretch was noted, this being greater for larger implants (>400 cc; p = 0.0011) and primary cases (p = 0.1376). Progressive volume redistribution from upper to lower pole was observed in the first year with substantial stability thereafter. CONCLUSIONS: This is the largest published series reporting long-term results (up to 45 months) in mastopexy augmentation with GalaFLEX, suggesting its supportive role in lower pole stability even in the setting of concurrent breast augmentation with smooth implants in a subfascial plane.

Local Energy Decomposition Analysis of London Dispersion Effects: From Simple Model Dimers to Complex Biomolecular Assemblies.

ConspectusLondon dispersion (LD) forces are ubiquitous in chemistry, playing a pivotal role in a wide range of chemical processes. For example, they influence the structure of molecular crystals, the selectivity of organocatalytic transformations, and the formation of biomolecular assemblies. Harnessing these forces for chemical applications requires consistent quantification of the LD energy across a broad and diverse spectrum of chemical scenarios. Despite the great progress made in recent years in the development of experimental strategies for LD quantification, quantum chemical methods remain one of the most useful tools in the hand of chemists for the study of these weak interactions. Unfortunately, the accurate quantification of LD effects in complex systems poses many challenges for electronic structure theories. One of the problems stems from the fact that LD forces originate from long-range electronic dynamic correlation, and hence, their rigorous description requires the use of complex, highly correlated wave function-based methods. These methods typically feature a steep scaling with the system size, limiting their applicability to small model systems. Another core challenge lies in disentangling short-range from long-range dynamic correlation, which from a rigorous quantum mechanical perspective is not possible.In this Account, we describe our research endeavors in the development of broadly applicable computational methods for LD quantification in molecular chemistry as well as challenging applications of these schemes in various domains of chemical research. Our strategy lies in the use of local correlation theories to reduce the computational cost associated with complex electronic structure methods while providing at the same time a simple means of decomposition of dynamic correlation into its long-range and short-range components. In particular, the local energy decomposition (LED) scheme at the domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) level has emerged as a powerful tool in our research, offering a clear-cut quantitative definition of the LD energy that remains valid across a plethora of different chemical scenarios. Typical applications of this scheme are examined, encompassing protein-ligand interactions and reactivity studies involving many fragments and complex electronic structures. In addition, our research also involves the development of novel cost-effective methodologies, which exploit the LED definition of the LD energy, for LD energy quantification that are, in principle, applicable to systems with thousands of atoms. The Hartree-Fock plus London Dispersion (HFLD) scheme, correcting the HF interaction energy using an approximate CCSD(T)-based LD energy, is a useful, parameter-free electronic structure method for the study of LD effects in systems with hundreds of molecular fragments. However, the usefulness of the LED scheme reaches beyond providing an interpretation of the calculated DLPNO-CCSD(T) or DLPNO-MP2 interaction energies. For example, the dispersion energies obtained from the LED can be fruitfully used in order to parametrize semiempirical dispersion models. We will demonstrate this in the context of an emerging semiempirical method, namely, the Natural Orbital Tied Constructed Hamiltonian (NOTCH) method. NOTCH incorporates LED-derived LD energies and shows promising accuracy at a minimum amount of empiricism. Thus, it holds substantial promise for large and complex systems.

Mechanism of Nitrous Oxide Activation in C(sp2)-O Bond Formation Reactions Catalyzed by Nickel Complexes.

Recent groundbreaking experimental reports demonstrated that Ni complexes bearing a bidentate- or tridentate-bipyridine-based ligand can be used to activate N2O for use as an O-transfer agent in C(sp2)-O bond formation reactions under mild experimental conditions. In this work, quantum chemical calculations are used to shed light on the mechanism through which such metal complexes catalytically activate nitrous oxide, providing new fundamental insights into the development of novel catalysts for N2O revalorization. As a case study, we consider the recent work by Cornella and co-workers (Nature, 2022, 604, 677) concerning the synthesis of phenols from aryl halides at room temperature, which requires the use of an external reducing agent. Our results suggest that the metal center remains in its Ni(II) oxidation state throughout the whole catalytic cycle, despite the presence of various redox steps in the mechanism and the Ni ability to maneuver between a number of oxidation states. This counterintuitive behavior is made possible by the ligand redox activity in the catalytic process, which involves accepting electrons from the reducing agent. Several possible pathways are systematically investigated, each associated with distinct activation modes, kinetics, and reaction outcomes. The governing factors in dictating the preferred path lie in the electronic nature of the ligand (strong vs weak field) and its geometric structure (specifically, the number of coordinating arms). These characteristics play a pivotal role in determining whether the process follows a catalytic or stoichiometric route and can be in principle modulated for the design of new metal complexes with tailored redox properties and reactivity.

Unraveling Atomic Contributions to the London Dispersion Energy: Insights into Molecular Recognition and Reactivity.

We present a general framework that enables quantification with atomic resolution of the overall London dispersion energy, which can be readily integrated with currently available energy decomposition schemes. This approach can be used to determine the contribution of individual atoms and functional groups to molecular recognition, conformational preferences, molecular stability, and reactivity. Its efficacy across diverse realms of molecular chemistry and biology is demonstrated with application to molecular balances in solution, asymmetric organocatalytic transformations, and a subcomplex of the F1FO ATP synthase.

Harnessing the electronic structure of active metals to lower the overpotential of the electrocatalytic oxygen evolution reaction.

Despite substantial advancements in the field of the electrocatalytic oxygen evolution reaction (OER), the efficiency of earth-abundant electrocatalysts remains far from ideal. The difficulty stems from the complex nature of the catalytic system, which limits our fundamental understanding of the process and thus the possibility of a rational improvement of performance. Herein, we shed light on the role played by the tunable 3d configuration of the metal centers in determining the OER catalytic activity by combining electrochemical and spectroscopic measurements with an experimentally validated computational protocol. One-dimensional coordination polymers based on Fe, Co and Ni held together by an oxonato linker were selected as a case study because of their well-defined electronic and geometric structure in the active site, which can be straightforwardly correlated with their catalytic activity. Novel heterobimetallic coordination polymers were also considered, in order to shed light on the cooperativity effects of different metals. Our results demonstrate the fundamental importance of electronic structure effects such as metal spin and oxidation state evolutions along the reaction profile to modulate ligand binding energies and increase catalyst efficiency. We demonstrated that these effects could in principle be exploited to reduce the overpotential of the electrocatalytic OER below its theoretical limit, and we provide basic principles for the development of coordination polymers with a tailored electronic structure and activity.

Elucidating the Electronic Nature of Rh-based Paddlewheel Catalysts from 103 Rh NMR Chemical Shifts: Insights from Quantum Mechanical Calculations.

The tremendous importance of dirhodium paddlewheel complexes for asymmetric catalysis is largely the result of an empirical optimization of the chiral ligand sphere about the bimetallic core. It was only recently that a H(C)Rh triple resonance 103 Rh NMR experiment provided the long-awaited opportunity to examine - with previously inconceivable accuracy - how variation of the ligands impacts on the electronic structure of such catalysts. The recorded effects are dramatic: formal replacement of only one out of eight O-atoms surrounding the metal centers in a dirhodium tetracarboxylate by an N-atom results in a shielding of the corresponding Rh-site of no less than 1000 ppm. The current paper provides the theoretical framework that allows this and related experimental observations made with a set of 19 representative rhodium complexes to be interpreted. In line with symmetry considerations, it is shown that the shielding tensor responds only to the donor ability of the equatorial ligands along the perpendicular principal axis. Axial ligands, in contrast, have no direct effect on shielding but may come into play via the electronic c i s ${cis}$ -effect that they exert onto the neighboring equatorial sites. On top of these fundamental interactions, charge redistribution within the core as well as the electronic t r a n s ${trans}$ -effect of ligands of different donor strengths is reflected in the recorded 103 Rh NMR shifts.

Dimerization of confined Brønsted acids in enantioselective organocatalytic reactions.

The formation of Brønsted acid aggregates in the course of asymmetric organocatalytic reactions is often overlooked in mechanistic studies, even though it might have a deep impact on the stereo-controlling factors of the transformations. In this work, we shed light on the influence of the catalyst structure and reaction conditions on the spontaneity of the aggregation process for popular chiral organocatalysts derived from phosphoric acids using high-level quantum mechanical calculations. Our study encompasses small and sterically unhindered chiral phosphoric acids as well as large and "confined" imidodiphosphates and imidodiphosphorimidates. These systems have recently proven particularly effective in promoting a large number of highly relevant asymmetric transformations. While cooperative catalytic effects of sterically less hindered chiral phosphoric acid catalysts are well appreciated in literature, it is found that the formation of catalyst dimers in solution is possible for both standard and confined catalysts. The spontaneity of the aggregation process depends on reaction conditions like solvent polarity, polarizability, temperature, the nature of the interaction with the substrate, as well as the catalyst architecture. Finally, it is shown that, at low temperatures (153 K), the aggregation process can profoundly influence the reaction kinetics and selectivity.

Taming secondary benzylic cations in catalytic asymmetric SN1 reactions.

Benzylic stereogenic centers are ubiquitous in natural products and pharmaceuticals. A potentially general, though challenging, approach toward their selective creation would be asymmetric unimolecular nucleophilic substitution (SN1) reactions that proceed through highly reactive benzylic cations. We now report a broadly applicable solution to this problem by identifying chiral counteranions that pair with secondary benzylic cations to engage in catalytic asymmetric C-C, C-O, and C-N bond-forming reactions with excellent enantioselectivity. The critical cationic intermediate can be accessed from different precursors via Lewis- or Brønsted acid catalysis. Key to our strategy is the use of only weakly basic, confined counteranions that are posited to prolong the lifetime of the carbocation, thereby avoiding nonproductive deprotonation pathways to the corresponding styrene.

Catalytic asymmetric synthesis of cannabinoids and menthol from neral.

The selective conversion of natural or synthetic neral to (1R,6S)-trans-isopiperitenol would enable and expedite sustainable routes to menthol1,2 and cannabinoids3-5. However, this reaction has been considered impossible because its product is more reactive to the required acid catalysts than its starting material, resulting in several side products6-9. We now show that an unsymmetric, strong and confined chiral acid, a highly fluorinated imino-imidodiphosphate, catalyses this process with excellent efficiency and selectivity. Expanding the method to other α,ß-unsaturated aldehydes could enable access to new cannabinoids and menthol derivatives not readily accessible previously. Mechanistic studies suggest that the confined catalyst accomplishes this reaction by binding the product in an unreactive conformation, thereby preventing its decomposition. We also show how (1R,6S)-trans-isopiperitenol can be readily converted to pharmaceutically useful cannabinoids and menthol, each in the shortest and most atom-economic routes so far.

Exploring the Accuracy Limits of PNO-Based Local Coupled-Cluster Calculations for Transition-Metal Complexes.

While the domain-based local pair natural orbital coupled-cluster method with singles, doubles, and perturbative triples (DLPNO-CCSD(T)) has proven instrumental for computing energies and properties of large and complex systems accurately, calculations on first-row transition metals with a complex electronic structure remain challenging. In this work, we identify and address the two main error sources that influence the DLPNO-CCSD(T) accuracy in this context, namely, (i) correlation effects from the 3s and 3p semicore orbitals and (ii) dynamic correlation-induced orbital relaxation (DCIOR) effects that are not described by the local MP2 guess. We present a computational strategy that allows us to completely eliminate the DLPNO error associated with semicore correlation effects, while increasing, at the same time, the efficiency of the method. As regards the DCIOR effects, we introduce a diagnostic for estimating the deviation between DLPNO-CCSD(T) and canonical CCSD(T) for systems with significant orbital relaxation.

Organocatalytic DYKAT of Si-Stereogenic Silanes.

Chiral organosilanes do not exist in nature and are therefore absent from the "chiral pool". As a consequence, synthetic approaches toward enantiopure silanes, stereogenic at silicon, are rather limited. While catalytic asymmetric desymmetrization reactions of symmetric organosilicon compounds have been developed, the utilization of racemic silanes in a dynamic kinetic asymmetric transformation (DYKAT) or dynamic kinetic resolution (DKR) would significantly expand the breadth of accessible Si-stereogenic compounds. We now report a DYKAT of racemic allyl silanes enabled by strong and confined imidodiphosphorimidate (IDPi) catalysts, providing access to Si-stereogenic silyl ethers. The products of this reaction are easily converted into useful enantiopure monohydrosilanes. We propose a spectroscopically and experimentally supported mechanism involving the epimerization of a catalyst-bound intermediate.

Exploring the Limits of Intramolecular London Dispersion Stabilization with Bulky Dispersion Energy Donors in Alkane Solution.

We present an experimental study of a cyclooctatetraene-based molecular balance disubstituted with increasingly bulky tert-butyl (tBu), adamantyl (Ad), and diamantyl (Dia) substituents in the 1,4-/1,6-positions for which we determined the valence-bond shift equilibrium in n-hexane (hex), n-octane (oct), and n-dodecane (dod). Computations including implicit and explicit solvation support our temperature-dependent NMR equilibrium measurements indicating that the more sterically crowded 1,6-isomer is always favored, irrespective of solvent, and that the free energy is quite insensitive to substituent size.

Synthetic Reabsorbable Mesh (GalaFLEX) as Soft Tissue Adjunct in Breast Augmentation Revision Surgery.

BACKGROUND: A significant number of patients with a previous submuscular breast augmentation require a revision surgical procedure during their long-term follow-up period that involves changing the implant pocket from submuscular to subglandular. Reduced soft tissue thickness represents a major concern, discouraging surgeons from undertaking this approach. OBJECTIVES: The aim of this study was to determine whether a synthetic resorbable mesh used as a supplemental covering device was safe and yielded improved soft tissue thickness and protection against capsular contracture in patients undergoing implant plane shift to subglandular. METHODS: A retrospective review of 34 patients who underwent revision of a previous breast augmentation involving implant change in a subglandular pocket and upper pole GalaFLEX (Galatea Surgical, BD; Franklin Lakes, NJ) mesh coverage was conducted. Onset of minor and major complications was recorded during short- and medium-term follow-up. Patient satisfaction was assessed via an anonymous questionnaire administered 6 months postoperatively. RESULTS: During the follow-up period, which ranged from a minimum of 6 months to a maximum of 28 months, no minor or major complications were reported. In particular, no wrinkling/rippling or significant capsular contracture onset was observed. High levels of patient satisfaction were determined, according to self-reporting questionnaires. CONCLUSIONS: The initial results of this preliminary report from this case series demonstrate the safety of GalaFLEX as a supplemental device in terms of improved soft tissue coverage of the implant for complex revisional cases in breast augmentation.

BIA-ALCL-Horizon Scanning.

BIA-ALCL is a subject that has dominated the world of breast implant surgery over the past 7 or 8 years. It is a controversial entity that has stoked much debate amongst the profession of plastic surgery and its associated scientific specialists. Whilst much has been learned about the disease, including its diagnosis, prognosis and treatment, there is still much debate related to aetiology and incidence. Experts remain divided on fundamental principles such as implant selection and appropriate advice to patients and expert bodies. The article is very much the authors' viewpoint based on the current literature and available data as it stands today.

An induced-fit model for asymmetric organocatalytic reactions: a case study of the activation of olefins via chiral Brønsted acid catalysts.

We elucidate the stereo-controlling factors of the asymmetric intramolecular hydroalkoxylation of terminal olefins catalyzed by bulky Brønsted acids [Science 2018, 359 (6383), 1501-1505] using high-level electronic structure methods. The catalyst-substrate interaction is described using a dispersion-driven induced-fit model, in which the conformational changes of the catalyst and of the substrate in the transition states are governed to a large extent by London dispersion forces. The distortion energy of the catalyst is dominated by the change in the intramolecular dispersion interactions, while intermolecular catalyst-substrate dispersion interactions are the major stabilizing contribution in the transition state. This model provides a new general framework in which to discuss the stereoselectivity of transformations catalyzed by such confined organocatalysts.

Experience and Indications for the Use of the P4HB Scaffold (GalaFLEX) in Aesthetic Breast Surgery: A 100-Case Experience.

BACKGROUND: The popularity of utilizing mesh in the breast has varied over the years. It is well described, and yet there has been poor uptake of its utilization in aesthetic breast surgery. Poly-4-huydroxybutarate (P4HB; GalaFLEX, Galatea, Lexington, MA) has recently been described as a useful adjunct in supporting poor tissue quality with positive early outcomes and low complication rates. OBJECTIVES: The authors sought to determine the outcome and range of indications of PH4B in aesthetic breast surgery to document its effectiveness in assisting with long-term outcomes in mastopexy. METHODS: Firstly, an observational study was undertaken standardizing mastopexy techniques with P4HB included in the procedure. Photographic measurements were taken to determine the extent of lower pole descent and lower pole stretch at 3 months and 1 year postoperative to observe change over time. Secondly, other indications were explored, including the correction of secondary defects such as inferior malposition and symmastia. RESULTS: The results of the mastopexy study were highly encouraging and comparable with those previously published in the literature, confirming sustained stability of the lower pole over time for mastopexies and implant mastopexies. In addition, the GalaFLEX was successfully employed in correcting many secondary defects. CONCLUSIONS: P4HB is extremely versatile and easy to utilize and has low complication rates. The results have led to a change in practice, with routine incorporation of GalaFLEX for all routine mastopexies. It has also replaced the utilization of acellular dermal matrices in aesthetic breast surgery.

Can domain-based local pair natural orbitals approaches accurately predict phosphorescence energies?

Since the discovery of the peculiar conducting and optical properties of aromatics, many efforts have been made to characterize and predict their phosphorescence. This physical process is exploited in modern Organic Emitting Light Diodes (OLEDs), and it is also one of the processes decreasing the efficiency of Dye-sensitized solar cells (DSSCs). Herein, we propose a computational strategy for the accurate calculation of singlet-triplet gaps of aromatic compounds, which provides results that are in excellent agreement with available experimental data. Our approach relies on the domain-based local pair natural orbital (DLPNO) variant of the "gold standard" CCSD(T) method. The convergence of our results with respect to the key technical parameters of the calculation, such as the basis set used, the approximations employed in the perturbative triples correction, and the dimension of the PNOs space, was thoroughly discussed.

Taming phosphorus mononitride.

Phosphorus mononitride (PN) only has a fleeting existence on Earth, and molecular precursors for the release of this molecule under mild conditions in solution have remained elusive. Here we report the synthesis of an anthracene-based precursor-an anthracene moiety featuring an azidophosphine bridge across its central ring-that dissociates into dinitrogen, anthracene and P≡N in solution with a first-order half-life of roughly 30 min at room temperature. Heated under reduced pressure, this azidophosphine-anthracene precursor decomposes in an explosive fashion at around 42 °C, as demonstrated in a molecular-beam mass spectrometry study. The precursor is also shown to serve as a PN transfer reagent in the synthesis of an Fe-NP coordination complex, through ligand exchange with its Fe-N2 counterpart. The terminal N-bonded complex was found to be energetically preferred, compared to its P-bonded linkage isomer, owing to a significant covalent Fe-pnictogen bond character and an associated less unfavourable Pauli repulsion in the metal-ligand interaction.

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation.

A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated and germylated) α-diazoacetate derivatives. A number of control experiments in combination with detailed computational studies provide compelling evidence that an interligand hydrogen bond between the -NH group of the amidate and the ester carbonyl group of the reactive rhodium carbene intermediate plays a quintessential role in the stereodetermining transition state. The penalty for distorting this array outweighs steric arguments and renders two of the four conceivable transitions states unviable. Based on this mechanistic insight, the design of the parent catalyst is revisited herein: placement of appropriate peripheral substituents allows high levels of diastereocontrol to be imposed upon cyclopropanation, which the original catalyst lacks. Because the new complexes allow either trans- or cis-configured stannylated cyclopropanes to be made selectively and in excellent optical purity, this transformation also marks a rare case of diastereodivergent asymmetric catalysis. The products are amenable to stereospecific cross coupling with aryl halides or alkenyl triflates; these transformations appear to be the first examples of the formation of stereogenic quaternary carbon centers by the Stille reaction; carbonylative coupling is also achieved. Moreover, tin/lithium exchange affords chiral lithium enolates, which can be intercepted with a variety of electrophilic partners. The virtues and inherent flexibility of this new methodology are illustrated by an efficient synthesis of two salinilactones, extremely scarce bacterial metabolites with signaling function involved in the self-regulatory growth inhibition of the producing strain.

A Combined Spectroscopic and Computational Study on the Mechanism of Iron-Catalyzed Aminofunctionalization of Olefins Using Hydroxylamine Derived N-O Reagent as the "Amino" Source and "Oxidant".

Herein, we study the mechanism of iron-catalyzed direct synthesis of unprotected aminoethers from olefins by a hydroxyl amine derived reagent using a wide range of analytical and spectroscopic techniques (Mössbauer, Electron Paramagnetic Resonance, Ultra-Violet Visible Spectroscopy, X-ray Absorption, Nuclear Resonance Vibrational Spectroscopy, and resonance Raman) along with high-level quantum chemical calculations. The hydroxyl amine derived triflic acid salt acts as the "oxidant" as well as "amino" group donor. It activates the high-spin Fe(II) (St = 2) catalyst [Fe(acac)2(H2O)2] (1) to generate a high-spin (St = 5/2) intermediate (Int I), which decays to a second intermediate (Int II) with St = 2. The analysis of spectroscopic and computational data leads to the formulation of Int I as [Fe(III)(acac)2-N-acyloxy] (an alkyl-peroxo-Fe(III) analogue). Furthermore, Int II is formed by N-O bond homolysis. However, it does not generate a high-valent Fe(IV)(NH) species (a Fe(IV)(O) analogue), but instead a high-spin Fe(III) center which is strongly antiferromagnetically coupled (J = -524 cm-1) to an iminyl radical, [Fe(III)(acac)2-NH·], giving St = 2. Though Fe(NH) complexes as isoelectronic surrogates to Fe(O) functionalities are known, detection of a high-spin Fe(III)-N-acyloxy intermediate (Int I), which undergoes N-O bond cleavage to generate the active iron-nitrogen intermediate (Int II), is unprecedented. Relative to Fe(IV)(O) centers, Int II features a weak elongated Fe-N bond which, together with the unpaired electron density along the Fe-N bond vector, helps to rationalize its propensity for N-transfer reactions onto styrenyl olefins, resulting in the overall formation of aminoethers. This study thus demonstrates the potential of utilizing the iron-coordinated nitrogen-centered radicals as powerful reactive intermediates in catalysis.